Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer.

OBJECTIVES: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC). METHODS: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC. RESULTS: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR). CONCLUSIONS: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.

Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity.

BACKGROUND: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. METHODS: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. RESULTS: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. CONCLUSION: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. METHODS: This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). RESULTS: In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. CONCLUSIONS: The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. CLINICAL RELEVANCE STATEMENT: This study's quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment.

Comprehensive analysis of the miRNA-mRNA regulatory network involved in spontaneous recovery of an H2O2-induced zebrafish cataract model.

OBJECTIVE: To identify the hub miRNAs and mRNAs contributing to the spontaneous recovery of an H2O2-induced zebrafish cataract model. METHODS: Zebrafishes were divided into three groups, i.e., Group A, which included normal control fish (day 0), and Groups B and C, where fish were injected with 2.5% hydrogen peroxide into the anterior chamber and reared for 14 and 30 days, respectively. Fish eyes were examined by stereomicroscope photography and optical coherence tomography (OCT). RNA profiles of fish lenses were detected by RNA sequencing. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were identified among three groups. The DEGs and DEmiRs, which changed in opposite positions between "B vs. A" and "C vs. B" were defined as ODGs (opposite positions changed DEGs) and ODmiRs (opposite positions changed DEmiRs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were carried out by R language. The protein-protein interaction network (PPI) was constructed using STRING. Potential targets of miRNAs were obtained using miRanda. miRNA-mRNA networks were constructed by Cytoscape. RESULTS: The fish lens opacity formed on day 14 and recovered to transparent on day 30 after injection. Compared to group B, 1366 DEGs and 54 DEmiRs were identified in group C. "C vs. B" DEGs were enriched in gene clusters related to development and oxidative phosphorylation. Target genes of DEmiRs were enriched in clusters such as development and cysteine metabolism. Among three groups, 786 ODGs and 27 ODmiRs were identified, and 480 ODGs were predicted as targets of ODmiRs. Target ODGs were enriched in pathways related to methionine metabolism, ubiquitin, sensory system development, and structural constituents of the eye lens. In addition, we established an ODmiRs-ODGs regulation network. CONCLUSION: We identified several hub mRNAs and altered miRNAs in the formation and reversal of zebrafish cataracts. These hub miRNAs/mRNAs could be potential targets for the non-surgical treatment of ARC.

Bayesian modeling of spatially differentiated multivariate enamel defects of the children's primary maxillary central incisor teeth.

BACKGROUND: The analysis of dental caries has been a major focus of recent work on modeling dental defect data. While a dental caries focus is of major importance in dental research, the examination of developmental defects which could also contribute at an early stage of dental caries formation, is also of potential interest. This paper proposes a set of methods which address the appearance of different combinations of defects across different tooth regions. In our modeling we assess the linkages between tooth region development and both the type of defect and associations with etiological predictors of the defects which could be influential at different times during the tooth crown development. METHODS: We develop different hierarchical model formulations under the Bayesian paradigm to assess exposures during primary central incisor (PMCI) tooth development and PMCI defects. We evaluate the Bayesian hierarchical models under various simulation scenarios to compare their performance with both simulated dental defect data and real data from a motivating application. RESULTS: The proposed model provides inference on identifying a subset of etiological predictors of an individual defect accounting for the correlation between tooth regions and on identifying a subset of etiological predictors for the joint effect of defects. Furthermore, the model provides inference on the correlation between the regions of the teeth as well as between the joint effect of the developmental enamel defects and dental caries. Simulation results show that the proposed model consistently yields steady inferences in identifying etiological biomarkers associated with the outcome of localized developmental enamel defects and dental caries under varying simulation scenarios as deemed by small mean square error (MSE) when comparing the simulation results to real application results. CONCLUSION: We evaluate the proposed model under varying simulation scenarios to develop a model for multivariate dental defects and dental caries assuming a flexible covariance structure that can handle regional and joint effects. The proposed model shed new light on methods for capturing inclusive predictors in different multivariate joint models under the same covariance structure and provides a natural extension to a nested hierarchical model.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

BACKGROUND. The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. OBJECTIVE. The purpose of this article is to investigate the impact of a minor (≤ 10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. METHODS. This retrospective study included 382 patients (mean age, 60.8 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015, and December 31, 2015, for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor ratio (CTR) of 0.9 to 1.0. Two radiologists independently assigned nodules to groups as either minor GGO (CTR, ≥ 0.9 and < 1.0) or pure solid (CTR = 1.0). Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. RESULTS. The two radiologists agreed for all nodules' classification into the minor-GGO (n = 106) or pure-solid (n = 276) groups. The mean CTR of the minor-GGO group was 0.93 ± 0.02 (SD) (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid-component diameter (2.68 vs 2.16 cm; p < .001) and total nodule diameter (2.89 vs 2.16 cm; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, p = .009) and pathologic lymph node involvement (4.7% vs 20.3%, p < .001), and EGFR mutation (71.6% vs 39.9%; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; p < .001) and higher frequency of better 5-year CSS (92.4% vs 76.4%, p = .004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR = 0.37, p = .001) but not with the likelihood of CSS. CONCLUSION. Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. CLINICAL IMPACT. Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

Radiographic characteristics of rifampicin-resistant tuberculosis in the STREAM stage 1 trial and their influence on time to culture conversion in the short regimen.

BACKGROUND: Stage 1 of the STREAM trial demonstrated that the 9 month (Short) regimen developed in Bangladesh was non-inferior to the 20 month (Long) 2011 World Health Organization recommended regimen. We assess the association between HIV infection and radiographic manifestations of tuberculosis and factors associated with time to culture conversion in Stage 1 of the STREAM trial. METHODS: Reading of chest radiographs was undertaken independently by two clinicians, and films with discordant reading were read by a third reader. Recording of abnormal opacity of the lung parenchyma included location (right upper, right lower, left upper, and left lower) and extent of disease (minimal, moderately-advanced, and far advanced). Time to culture conversion was defined as the number of days from initiation of treatment to the first of two consecutive negative culture results, and compared using the log-rank test, stratified by country. Cox proportional hazards models, stratified by country and adjusted for HIV status, were used to identify factors associated with culture conversion. RESULTS: Of the 364 participants, all but one had an abnormal chest X-ray: 347 (95%) had opacities over upper lung fields, 318 (87%) had opacities over lower lung fields, 124 (34%) had far advanced pulmonary involvement, and 281 (77%) had cavitation. There was no significant association between HIV and locations of lung parenchymal opacities, extent of opacities, the presence of cavitation, and location of cavitation. Participants infected with HIV were significantly less likely to have the highest positivity grade (3+) of sputum culture (p = 0.035) as compared to participants not infected with HIV. Cavitation was significantly associated with high smear positivity grades (p < 0.001) and high culture positivity grades (p = 0.004) among all participants. Co-infection with HIV was associated with a shorter time to culture conversion (hazard ratio 1.59, 95% CI 1.05-2.40). CONCLUSIONS: Radiographic manifestations of tuberculosis among the HIV-infected in the era of anti-retroviral therapy may not differ from that among those who were not infected with HIV. Radiographic manifestations were not consistently associated with time to culture conversion, perhaps indicating that the Short regimen is sufficiently powerful in achieving sputum conversion across the spectrum of radiographic pulmonary involvements. TRIAL REGISTRATION: ISRCTN ISRCTN78372190. Registered 14/10/2010. The date of first registration 10/02/2016.

Trichromatic critical flicker frequency as potential visual test in cataract and macula disease patients.

PURPOSE: To investigate the capacity of critical flicker frequency (CFF) in discriminating cataract eyes with or without macula disease using trichromatic flickers, and to develop a model to predict postoperative best corrected visual acuity (BCVA). METHODS: Patients were divided into two groups based on the presence or absence of macular disease. CFF threshold measurements of red (R-CFF), green (G-CFF), and yellow (Y-CFF) flickers were conducted both preoperatively and postoperatively. A generalized estimating equations model (GEE) was employed to examine the relationship between CFF threshold and 3-month postoperative BCVA. RESULTS: A total of 115 eyes were enrolled, with 59 eyes in the cataract alone group and 56 eyes in the cataract with macular disease group completing the follow-up. R-CFF was found to be consistent before and after cataract removal (P = 0.06), even in cases where OCT was not performed successfully (P > 0.05). Y-CFF showed the highest AUC (0.798) for differentiating ocular comorbidities. According to the GEE model, in patients with a CFF threshold below 26 Hz, the odds ratios for achieving a postoperative VA of 20/40 or better were 34.8% for R-CFF, 26.0% for G-CFF, and 24.5% for Y-CFF. CONCLUSION: CFF emerges as a promising tool for predicting postoperative BCVA, providing valuable supplementary insights when fundus examination is obstructed. R-CFF demonstrates the best resistance to cataracts, while Y-CFF exhibits the highest sensitivity both in identifying macular diseases and predicting postoperative BCVA of 20/40 or better.

Diagnostic Accuracy and Safety of Nonsurgical Biopsy for Diagnosing Pulmonary Ground-Glass Opacities: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous meta-analyses have explored the diagnostic accuracy and safety of computed tomography-guided percutaneous lung biopsy of ground-glass opacities (GGOs). However, no research investigated the role of nonsurgical biopsies (including transbronchial approaches). Additionally, studies reporting the diagnostic accuracy of GGOs with different characteristics are scarce, with no quantitative assessment published to date. We performed a systematic review to explore the diagnostic accuracy and safety of nonsurgical biopsy for diagnosing GGOs, especially those with higher ground-glass components and smaller nodule sizes. METHODS: A thorough literature search of four databases was performed to compile studies evaluating both or either of the diagnostic accuracy and complications of nonsurgical biopsy for GGOs. A bivariate random-effects model and random-effect model were utilized for data synthesis. The methodological quality of the studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: Nineteen eligible studies with a total of 1,379 biopsy-sampled lesions were analyzed, of which 1,124 were confirmed to be malignant. Nonsurgical biopsy reported a pooled sensitivity of 0.89, a specificity of 0.99, and a negative predictive value (NPV) of 60.3%. The overall sensitivity, specificity, and NPV of nonsurgical biopsy for diagnosing GGOs according to GGO component were 0.90, 0.99, and 77.2% in pure GGOs; 0.87, 0.99, and 67.2% in GG-predominant lesions; and 0.89, 1.00, and 44.1% in solid-predominant lesions, respectively. Additionally, the diagnostic sensitivity was better in lesions ≥20 mm than in small lesions (0.95 vs. 0.88). Factors that contributed to higher sensitivity were the use of a coaxial needle system and CT fluoroscopy but not the needle gauge. The summary sensitivity of core needle biopsy (CNB) was not significantly higher than fine needle aspiration (FNA) (0.92 vs. 0.84; p = 0.42); however, we found an increased incidence of hemorrhage in CNB compared with FNA (60.9 vs. 14.2%; p = 0.012). CONCLUSION: Nonsurgical biopsy for diagnosing GGOs shows high sensitivity and specificity with an acceptably low risk of complications. However, negative biopsy results are unreliable in excluding malignancy, necessitating resampling or subsequent follow-up. The applicability of our study is limited due to significant heterogeneity, indirect comparisons, and the paucity of data on bronchoscopic approaches, restricting the generalizability of our findings to patients requiring transbronchial biopsies.

Classifications of anterior segment structure of congenital corneal opacity in infants and toddlers by ultrasound biomicroscopy and slit-lamp microscopic photographs: an observational study.

BACKGROUND: The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity. METHODS: Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed. RESULTS: Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003). CONCLUSIONS: This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.

Juvenile ocular abnormalities in a litter of black-footed ferrets.

OBJECTIVE: To describe the clinical and histopathological features of ocular abnormalities noted in a litter of black-footed ferrets (Mustela nigripes), including corneal opacification, cataracts, persistent pupillary membranes, microphthalmia, symblepharon and anterior segment malformation. ANIMALS STUDIED: A litter of eight black-footed ferrets examined at 10 weeks old with a history of ophthalmia neonatorum first noted at 7 days old and histopathological examination of three globes from three ferrets of the same litter between 5 and 7 months old following routine subconjunctival enucleation. PROCEDURES: Due to the fractious nature of black-footed ferrets, slit-lamp biomicroscopic examination was performed under general isoflurane anesthesia at 10 weeks of age. Corneal opacification was noted in 9/16 eyes, cataracts in 4/16 eyes, and persistent pupillary membranes in 3/16 eyes, among other findings. Histopathology revealed persistent pupillary membranes and Descemet's membrane abnormalities consistent with congenital anterior segment malformation in all three globes. In one ferret, a posterior cortical cataract with posterior lenticular malformation and lens capsule discontinuity was noted. Purulent discharge was cultured at time of enucleation in one ferret with growth of E. coli. CONCLUSIONS: A novel constellation of ocular malformations with primary congenital and secondary to ophthalmia neonatorum etiologies is described in black-footed ferrets. Due to endangered status of black-footed ferrets, small genetic pool and the requirement for adequate vision for wild-release, congenital ocular abnormalities such as anterior segment malformation and likely the cataracts described are of particular concern. Further investigation and monitoring are warranted to determine the heritability of these ocular abnormalities.

Influence of Ca3(PO4)2 on the Surface Morphology and Properties of a CaO-Al2O3-SiO2-Fe2O3-Based High Temperature Phase Reconstructed Complex.

In this study, a glaze slurry was prepared with different contents of tricalcium phosphate. It was then applied to a fly ash microcrystalline ceramic billet and sintered at 1180 °C for 30 min to prepare the complex. The aim was to obtain a high value-added application of fly ash in order to reduce environmental pollution. The study systematically investigated the influence of the Ca3(PO4)2 content on the crystal phase evolution, physical-mechanical properties, and micro-morphology of the complex. The results showed that products sintered at 1180 °C with 8 wt% Ca3(PO4)2 demonstrated better performance, with a water absorption of 0.03% and a Vickers microhardness of 6.5 GPa. Additionally, the study observed a strong correlation between the Ca3(PO4)2 content and the opacity effect. A feasible opacity mechanism was also proposed to explain the variation of glaze colors and patterns with different contents of Ca3(PO4)2.

Ocular irritation reversibility assessment of a laundry detergent using the Porcine Corneal Opacity Reversibility Assay (PorCORA): a focused study.

Consumer product manufacturers utilise a spectrum of alternative ocular irritation assays, as these tests do not require the use of live animals. Despite their usefulness, no regulatory-accepted assay assesses the reversibility of ocular damage, a key criterion of GHS ocular classification, like the rabbit eye test (i.e., Draize Rabbit Eye Test [DRET]) . The Porcine Corneal Opacity Reversibility Assay (PorCORA), an ex vivo intact corneal tissue culture model, predicts the reversibility of damage by ocular irritants. Inclusion of the damage reversibility endpoint in the PorCORA supplements other alternative test methods for ocular irritation, by assessing induced eye damage and the ability of this damage to reverse (heal) without the use of live animals to distinguish between Globally Harmonised System of Classification and Labelling of Chemicals (GHS) ocular classifications. In this focused study, results of a Bovine Corneal Opacity and Permeability (BCOP) test of a laundry detergent, neat and 10% dilution, (product mixture from S.C. Johnson & Son, Inc. [SCJ]) classified the product into GHS Category 1; however, the BCOP test cannot assess the reversibility of ocular damage. The laundry detergent was evaluated using the PorCORA, where ocular damage induced by the detergent was fully reversed within seven days. Evaluation of the reversibility of ocular damage using the PorCORA in this focused study can add strength to the weight-of-evidence (WoE) analysis approach in ocular hazard assessment. This WoE approach strengthens the argument that the PorCORA can be used to supplement BCOP data, and that this laundry detergent is not an irreversible eye irritant.

Evaluation of eye irritation potential of experimental cosmetic formulations containing glycolic acid, salicylic acid and ethanol using the Bovine Corneal Opacity and Permeability Assay.

OBJECTIVE: Prototype cosmetic formulations containing short-chain acids and alcohols intended to be applied in the proximity of the eyes are sometimes evaluated for ocular irritation potential using the validated Bovine Corneal Opacity and Permeability Assay (OECD TG 437). We evaluated the eye irritation potential of nine experimental cosmetic formulations designed and prepared by Avon Global Reserach and Development to differ only in the concentrations of Ethanol, Glycolic Acid and Salicylic Acid. METHODS: We analysed the data generated using the BCOP assay. The opacity and permeability values obtained following the exposure of bovine corneas to experimental cosmetic formulations were combined into a single In Vitro Irritancy Score used to rank eye irritation potential. Histopathological examination of treated corneas was used to provide additional information about the depth and degree of the injury and to support the prediction of eye irritation potential of each experimental cosmetic formulation. RESULTS: The In Vitro Irritancy Scores and histopathological analysis showed that experimental formulations containing only Ethanol, Glycolic Acid, or Salicylic Acid alone had, at most, a mild ocular irritation potential. The experimental formulations containing both Ethanol and Glycolic Acid had a mild ocular irritation potential, while the experimental formulations containing both Ethanol and Salicylic Acid had a moderate ocular irritation potential. Severe ocular irritation potential was induced by an experimental formulation containing a combination of Glycolic Acid and Salicylic Acid and it was further accentuated by the addition of Ethanol to the formulation. Our data indicate a possible synergistic effect on eye irritation potential of Ethanol, Glycolic Acid and Salicylic Acid in at least some experimental cosmetic formulations. Further, our results provide insight on an apparent concentration-dependent ocular irritation potential effect of combinations of Glycolic Acid, Salicylic Acid and Ethanol in at least one experimental cosmetic formulation. CONCLUSIONS: The results presented herein emphasise the need to consider in vitro testing of prototype cosmetic formulations containing combinations of Ethanol, Glycolic Acid and Salicylic Acid rather than relying on any predicted additive effect on ocular irritation based solely on previously generated results of similar formulations containing Ethanol, Glycolic Acid or Salicylic Acid alone. Further work is required to understand the significance of these observations and to elucidate the mechanisms responsible for the apparent synergistic effects of Glycolic Acid, Salicylic Acid and Ethanol and eye irritation potential suggested by our results.

Effect of dry and wet finishing and polishing on color change and opacity of nanofill and nanohybrid composites.

BACKGROUND: As superior esthetic is one of the main reasons for using composite resins, it is very important to be familiar with factors and techniques affecting their optical properties and appearance. AIM: The aim of this study was comparing the effect of finishing and polishing with and without water coolant, on the color change and opacity of composite resin materials. METHODS: Composites used for preparing samples were Z250 (microhybrid), Z350XT (nanofilled), and Z550 (nanohybrid). Then divided into 4 groups of 5 depending on finishing and polishing technique (dry or wet) and time (immediate and after twenty-four hours). After polishing, samples were assessed using a spectrophotometer. Color change and opacity were determined. Data was analyzed using Kolmogorov-Smirnov, ANOVA and Tukey HSD tests. RESULTS: Type of material at both time had a significant effect on ΔE and opacity. Our results in dry and wet technique immediately(T0) showed that the highest and lowest ΔE and opacity belong to Z350XT (p < 0.001). After Twenty-four hours (T24), opacity of Z250 in wet condition was higher than dry condition (p < 0.001). CONCLUSIONS: Wet or dry technique was only effective on color in immediate polishing. Regarding opacity, technique was only effective in case of delayed polishing.

CT quantification of COVID-19 pneumonia extent to predict individualized outcome.

OBJECTIVES:  This study aimed to predict individual COVID-19 patient prognosis at hospital admission using artificial intelligence (AI)-based quantification of computed tomography (CT) pulmonary involvement. BACKGROUND: Assessing patient prognosis in COVID-19 pneumonia is crucial for patient management and hospital and ICU organization. METHODS: We retrospectively analyzed 559 patients with PCR-verified COVID-19 pneumonia referred to the hospital for a severe disease course. We correlated the CT extent of pulmonary involvement with patient outcome. We also attempted to define cut-off values of pulmonary involvement for predicting different outcomes. RESULTS:  CT-based disease extent quantification is an independent predictor of patient morbidity and mortality, with the prognosis being impacted also by age and cardiovascular comorbidities. With the use of explored cut-off values, we divided patients into three groups based on their extent of disease: (1) less than 28 % (sensitivity 65.4 %; specificity 89.1 %), (2) ranging from 28 % (31 %) to 47 % (sensitivity 87.1 %; specificity 62.7 %), and (3) above 47 % (sensitivity 87.1 %; specificity, 62.7 %), representing low risk, risk for oxygen therapy and invasive pulmonary ventilation, and risk of death, respectively. CONCLUSION: CT quantification of pulmonary involvement using AI-based software helps predict COVID-19 patient outcomes (Tab. 4, Fig. 4, Ref. 38).

Serum opacity factor rescues fertility among female Scarb1-/- mice by reducing HDL-free cholesterol bioavailability.

Human female infertility, 20% of which is idiopathic, is a public health problem for which better diagnostics and therapeutics are needed. A novel cause of infertility emerged from studies of female mice deficient in the HDL receptor gene (Scarb1). These mice are infertile and have high plasma HDL cholesterol (C) concentrations, due to elevated HDL-free cholesterol (FC), which transfers from HDL to all tissues. Previous studies have indicated that oral delivery of probucol, an HDL-lowering drug, to female Scarb1-/- mice reduces plasma HDL-C concentrations and rescues fertility. Additionally, serum opacity factor (SOF), a bacterial virulence factor, disrupts HDL structure, and bolus SOF injection into mice reduces plasma HDL-C concentrations. Here, we discovered that delivering SOF to female Scarb1-/- mice with an adeno-associated virus (AAVSOF) induces constitutive SOF expression, reduces HDL-FC concentrations, and rescues fertility while normalizing ovary morphology. Although AAVSOF did not alter ovary-FC content, the ovary-mol% FC correlated with plasma HDL-mol% FC in a fertility-dependent way. Therefore, reversing the abnormal plasma microenvironment of high plasma HDL-mol% FC in female Scarb1-/- mice rescues fertility. These data provide the rationale to search for similar mechanistic links between HDL-mol% FC and infertility and the rescue of fertility in women by reducing plasma HDL-mol% FC.

Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.

The lens is transparent, non-vascular, elastic and wrapped in a transparent capsule. The lens oppacity of AQP5-/- mice was increased more than that of wild-type (AQP5+/+ ) mice. In this study, we explored the potential functional role of circular RNAs (circRNAs) and transcription factor HSF4 in lens opacity in aquaporin 5 (AQP5) knockout (AQP5-/- ) mice. Autophagy was impaired in the lens tissues of AQP5-/- mice. Autophagic lysosomes in lens epithelial cells of AQP5-/- mice were increased compared with AQP5+/+ mice, based on analysis by transmission electron microscopy. The genetic information of the mice lens was obtained by high-throughput sequencing, and then the downstream genes were analysed. A circRNA-miRNA-mRNA network related to lysosomal pathway was constructed by the bioinformatics analysis of the differentially expressed circRNAs. Based on the prediction of the TargetScan website and the validation by dual luciferase reporter assay and RNA immunoprecipitation-qPCR, we found that circRNA (Chr16: 33421321-33468183+) inhibited the function of HSF4 by sponging microRNA (miR-149-5p), and it downregulated the normal expression of lysosome-related mRNAs. The accumulation of autophagic lysosome may be one of the reasons for the abnormal development of the lens in AQP5-/- mice.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.